Professor Ravindra Gupta of University College London presented the case
on Tuesday, but after a premature embargo break the day before, many media
outlets reported the findings in advance, with some suggesting that the case
represents a second HIV cure, similar to that of Timothy Ray Brown, known as
the 'Berlin patient'.

Brown – the first and
so far only person known to have been cured of HIV – received two stem cell transplants to
treat leukaemia in 2006. The donor had double copies of a rare gene mutation
known as CCR5-delta-32 that results in missing CCR5 co-receptors on T cells,
the gateway most types of HIV use to infect cells. He underwent
intensive conditioning chemotherapy and whole-body radiation therapy to kill
off his cancerous immune cells, allowing the donor stem cells to rebuild a new HIV-resistant
immune system.

As described at the 2007 CROI, Brown stopped antiretroviral
therapy at the time of his first transplant but his viral load did not rebound.
Researchers extensively tested his blood, gut, brain and other tissues, finding
no evidence of replication-competent HIV anywhere in his body. This week Brown
celebrated 12 years free of HIV and was at CROI to hear about the 'London patient'.

Other attempts to discontinue antiretroviral therapy in
HIV-positive bone marrow transplant recipients have been less successful. Dr Timothy
Henrich, now at the University of California at San Francisco, and colleagues attempted
to reproduce Brown's cure in two cancer patients in Boston, but in those cases
the donors had normal or 'wild-type' stem cells that remained susceptible to HIV, they
received less intensive chemotherapy and they stayed on antiretroviral therapy.

After no HIV could be detected in their blood and tissues for years, the
men underwent closely monitored treatment interruptions. Although their HIV
remained in remission longer than expected – for three and eight months – eventually their virus returned, Henrich reported
at CROI 2014. More recently, researchers reported that a bone marrow transplant
recipient in Minnesota had viral remission lasting nearly 10 months after an
analytic treatment interruption, but he too ultimately experienced viral rebound.

"The work we did involved cells that were susceptible to HIV, but even
then we saw a dramatic reduction in the size of the HIV reservoir and a
prolonged rebound time, suggesting that the transplant itself can reduce the
burden of HIV," Henrich told aidsmap. "But adding this piece where
the cells are resistant to the patient's strain of HIV really makes the
difference to go the whole hundred yards."

The so-called 'London patient', who remains anonymous, underwent stem cell
transplantation to treat Hodgkin lymphoma in May 2016. Like Brown, his donor
had a double CCR5-delta-32 mutation.

The man continued on his antiretroviral regimen of dolutegravir (Tivicay), rilpivirine (Edurant) and lamivudine. He also received
less aggressive conditioning chemotherapy (lomustine, cyclophosphamide,
cytarabine and etoposide), alemtuzumab (Campath,
a monoclonal antibody that targets CD52 on malignant B and T cells), and cyclosporine-A
and methotrexate, immunosuppressive drugs used to prevent graft-versus-host
disease (when transplanted immune cells attack the recipient's body).

The transplant led to complete lymphoma remission. About 10 weeks
post-transplant the man developed mild graft-versus-host disease, which
resolved on its own. He also experienced reactivation of pre-existing
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection, which were
treated. Tests showed that his CD4 T cells now lacked CCR5 receptors. Extensive
testing of blood plasma and T cells revealed undetectable HIV and his
HIV-specific antibody levels also dropped.

The man stopped antiretroviral therapy in an analytic treatment
interruption 16 months after the transplant. His blood viral load remains
undetectable 18 months later using a sensitive assay with a 1 copy/ml limit, no
HIV DNA can be found in peripheral CD4 cells and tests showed no "reactivatable"
virus in 24 million resting T cells. One blood sample revealed bits of viral
genetic material, which may reflect laboratory contamination or defective virus
that is unable to replicate, Gupta suggested. Unlike Brown, the London patient
has not yet undergone testing for residual HIV in his gut, brain and other
tissues.

These findings demonstrate that "the Berlin patient was not
an anomaly," Gupta said. What's more, this case shows that remission can
happen without harsh conditioning chemotherapy or radiation therapy. While this
appears to be the second longest adult HIV remission yet observed, the researchers acknowledge that "it is
premature to conclude that this patient has been cured."

Gupta noted that the man's HIV viral load could still rebound.
He suggested that two or three years without detectable virus would be enough
time to speak of a cure, saying he was "highly confident this will be
achieved."

A poster presented at CROI described another case of long-term HIV
remission after a stem cell transplant from a donor with a double CCR5-delta-32
mutation. This patient, treated in Dusseldorf, underwent the procedure in February
2013 to treat acute myeloid leukaemia. The man remained on antiretroviral
therapy with undetectable viral load until November 2018. Extensive testing
showed no viral DNA in his bone marrow, gut tissue samples, rectal tissue
samples or lymph nodes. The Dusseldorf patient stopped antiretroviral therapy
in November 2018, still has undetectable
HIV and is undergoing continued monitoring.

Experts
caution that even if CCR5-delta-32 stem cell transplantation can lead to a
functional cure of HIV, this high-risk procedure will not be an option for most
people.

"This is
not a treatment appropriate for people with HIV who do not have cancer,"
the Treatment Action Group said in a statement. "The hope is that lessons
can be learned to help develop more widely applicable therapeutic approaches
for attaining HIV remissions or cures."

Stem
cell transplantation is life-threatening, with a mortality rate of 10 to 25%. Brown
nearly died during the process and was left with lasting side-effects. However,
this new case adds to the evidence that using gene therapy to delete CCR5
receptors from T cells may be a feasible approach.

"I think it's getting close to something that should be called a
cure," Brown told aidsmap. "I consider him my sibling and I can't wait
to meet him."

This report, originally posted on 4 March 2019,
has been updated to reflect new information presented at CROI on 5 March.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.